TY - JOUR
T1 - Varicella Zoster Virus Impairs Expression of the Nonclassical Major Histocompatibility Complex Class I-Related Gene Protein (MR1)
AU - Purohit, Shivam K.
AU - Samer, Carolyn
AU - McWilliam, Hamish E.G.
AU - Traves, Renee
AU - Steain, Megan
AU - McSharry, Brian P.
AU - Kinchington, Paul R.
AU - Tscharke, David C.
AU - Villadangos, Jose A.
AU - Rossjohn, Jamie
AU - Abendroth, Allison
AU - Slobedman, Barry
N1 - Publisher Copyright:
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - The antigen presentation molecule MR1 (major histocompatibility complex, class I-related) presents ligands derived from the riboflavin (vitamin B) synthesis pathway, which is not present in mammalian species or viruses, to mucosal-associated invariant T (MAIT) cells. In this study, we demonstrate that varicella zoster virus (VZV) profoundly suppresses MR1 expression. We show that VZV targets the intracellular reservoir of immature MR1 for degradation, while preexisting, ligand-bound cell surface MR1 is protected from such targeting, thereby highlighting an intricate temporal relationship between infection and ligand availability. We also identify VZV open reading frame (ORF) 66 as functioning to suppress MR1 expression when this viral protein is expressed during transient transfection, but this is not apparent during infection with a VZV mutant virus lacking ORF66 expression. This indicates that VZV is likely to encode multiple viral genes that target MR1. Overall, we identify an immunomodulatory function of VZV whereby infection suppresses the MR1 biosynthesis pathway.
AB - The antigen presentation molecule MR1 (major histocompatibility complex, class I-related) presents ligands derived from the riboflavin (vitamin B) synthesis pathway, which is not present in mammalian species or viruses, to mucosal-associated invariant T (MAIT) cells. In this study, we demonstrate that varicella zoster virus (VZV) profoundly suppresses MR1 expression. We show that VZV targets the intracellular reservoir of immature MR1 for degradation, while preexisting, ligand-bound cell surface MR1 is protected from such targeting, thereby highlighting an intricate temporal relationship between infection and ligand availability. We also identify VZV open reading frame (ORF) 66 as functioning to suppress MR1 expression when this viral protein is expressed during transient transfection, but this is not apparent during infection with a VZV mutant virus lacking ORF66 expression. This indicates that VZV is likely to encode multiple viral genes that target MR1. Overall, we identify an immunomodulatory function of VZV whereby infection suppresses the MR1 biosynthesis pathway.
KW - MR1
KW - VZV
KW - immune modulation
KW - varicella zoster virus
UR - http://www.scopus.com/inward/record.url?scp=85147317504&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiab526
DO - 10.1093/infdis/jiab526
M3 - Article
SN - 0022-1899
VL - 227
SP - 391
EP - 401
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -